Nerve Cells Research Articles

All-organic nanocomposite with strong photo-pyroelectric response and its application in retinal prosthesis

In patients with retinal degenerative diseases, vision restoration is feasible through implanted artificial retinal prostheses to stimulate surviving neurons. Photoelectric composites based on ferroelectric polymers have been attempted to construct retinal prostheses. However, these materials normally have a low photoelectric response and a narrow response wavelength range. Here, we synthesize conjugated poly-Schiff base nanoparticles with ultra-small size, and the nanocomposites of the nanoparticles and poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ferroelectric polymer generate a high photoelectric response (maximum peak-to-peak voltage > 90 V) under visible and near-infrared light. This flexible all-organic nanocomposite has good biocompatibility and can establish effective signal transduction with neuron cells. We explored the use of composites to construct ferroelectric retinal prostheses. Electrophysiological tests and animal behavior analysis have preliminary shown that implanted retinal prostheses can restore the visible light sensitivity of blind rats and further endow them with the ability to perceive infrared light, demonstrating their potential application in bioelectronics. This work presents a novel all-organic ferroelectric polymer composite with flexibility, biocompatibility, and excellent photoelectric response that can be used for artificial retinal prostheses. The nanocomposite composed of ultra-small conjugated nanoparticles and ferroelectric P(VDF-TrFE) exhibits excellent photo-pyroelectric response under visible and infrared light, with a peak-to-peak voltage exceeding 90 V. The ultra-thin retinal prostheses (∼ 20 µm) constructed from this nanocomposite can directly stimulate nerve cells, effectively restore the visual function of blind rats, and endow them with infrared light sensitivity.

Oligodendroglioma: a neurological perspective in Sub-saharan Africa.

Gliomas are a kind of brain cancer that develops from glial cells. Glial cells provide nourishment and energy to nerve cells, and they also preserve the blood-brain barrier. A primary cancer of the central nervous system (CNS) is oligodendroglioma. This suggests that it originates in the brain or spinal cord. While oligodendrogliomas can strike anyone at any age, the age range of 35 to 44 is when they most commonly occur. Oligodendrogliomas are rare in young people and more common in men than women. Based on anecdotal data, patients with oligodendroglioma may present management challenges in Africa. There are delays in diagnosis and referrals due to the scarcity of neuroimaging facilities. A wide range of strategies have been put forth to improve pathology services in low- and middle-income nations. Adequate mentorship, short-term visitor programs, overcoming supply chain constraints, establishing training standards, and establishing the role of pathologists in cancer screening and early diagnosis have all been proposed as solutions to this problem. To sum up, oligodendroglioma is one of the low-grade gliomas this study looked at. Brain cancer is a serious public health concern in Africa. Improved options for screening and therapy are required to better address this problem.

A NSC-34 cell line-derived spheroid model: Potential and challenges for in vitro evaluation of neurodegeneration.

Three-dimensional (3D) spheroid models aim to bridge the gap between traditional two-dimensional (2D) cultures and the complex in vivo tissue environment. These models, created by self-clustering cells to mimic a 3D environment with surrounding extracellular framework, provide a valuable research tool. The NSC-34 cell line, generated by fusing mouse spinal cord motor neurons and neuroblastoma cells, is essential for studying neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), where abnormal protein accumulation, such as TAR-DNA-binding protein 43 (TDP-43), occurs in affected nerve cells. However, NSC-34 behavior in a 3D context remains underexplored, and this study represents the first attempt to create a 3D model to determine its suitability for studying pathology. We generated NSC-34 spheroids using a nonadhesive hydrogel-based template and characterized them for 6 days. Light microscopy revealed that NSC-34 cells in 3D maintained high viability, a distinct round shape, and forming stable membrane connections. Scanning electron microscopy identified multiple tunnel-like structures, while ultrastructural analysis highlighted nuclear bending and mitochondria alterations. Using inducible GFP-TDP-43-expressing NSC-34 spheroids, we explored whether 3D structure affected TDP-43 expression, localization, and aggregation. Spheroids displayed nuclear GFP-TDP-43 expression, albeit at a reduced level compared with 2D cultures and generated both TDP-35 fragments and TDP-43 aggregates. This study sheds light on the distinctive behavior of NSC-34 in 3D culture, suggesting caution in the use of the 3D model for ALS or TDP-43 pathologies. Yet, it underscores the spheroids' potential for investigating fundamental cellular mechanisms, cell adaptation in a 3D context, future bioreactor applications, and drug penetration studies. RESEARCH HIGHLIGHTS: 3D spheroid generation: NSC-34 spheroids, developed using a hydrogel-based template, showed high viability and distinct shapes for 6 days. Structural features: advanced microscopy identified tunnel-like structures and nuclear and mitochondrial changes in the spheroids. Protein dynamics: the study observed how 3D structures impact TDP-43 behavior, with altered expression but similar aggregation patterns to 2D cultures. Research implications: this study reveals the unique behavior of NSC-34 in 3D culture, suggests a careful approach to use this model for ALS or TDP-43 pathologies, and highlights its potential in cellular mechanism research and drug testing applications.

A Comparative Study on Data Balancing Methods for Alzheimer's Disease Classification

Alzheimer's disease is a prevalent neurological disorder affecting millions of people worldwide, often associated with the aging process, leading to the death of nerve cells in the brain and loss of connections. Recently, promising results have been demonstrated in diagnosing Alzheimer's disease using deep learning models, and various approaches for early diagnosis have been proposed. However, the imbalance in health datasets, particularly those containing rare cases, can lead to performance losses and misleading results during model training. This study focuses on these imbalance issues, evaluating the effectiveness of different balancing methods using the Alzheimer's MRI dataset. In this context, the performance of SMOTE, ADASYN, and Weight Balancing methods is compared using a custom model. Experimental results indicate that, compared to the original imbalanced dataset, Weight balancing outperforms in terms of accuracy, precision, recall, and F1 score. While SMOTE and ADASYN show improvement in various metrics, they are considered inferior to the Weight Balancing method. This study contributes to selecting data-balancing methods to enhance the accuracy of deep learning models in Alzheimer's disease classification and emphasizes the importance of addressing class imbalances in health datasets.

Management of Parkinson’s Disease (Kampavata) Through Panchakarma

Parkinson's disease is a progressive degenerative neurological disorder mainly affecting geriatric population. The most crucial signs and symptoms of Parkinson’s disease arise while the nerve cells in basal ganglia, an area of mind that controls the movement grow to be impaired or die. When these neurons die or get impaired, they generally tend to produce much less amount of vital chemical in the brain known as Dopamine which causes numerous signs and symptoms like tremors, rigidity in muscular tissues, akinesia and postural disability related to numerous cognitive, behavioural and other mental signs. In Ayurveda due to similar disease presentation, Parkinson's disease can be compared with Kampavata. Kampavata has been described under Vataja Nanatmaja Vyadhi. Various Panchakarma therapies have been mentioned in classics for the treatment of Kampavata like Abhyanga, Swedana, Niruha Basti, Anuvasana Basti, Shirobasti and Virechana. In this case study, a 68 years old male patient came to ITRA Hospital having complaints of tremors in both upper limbs, difficulty in speech and slowness of movements since last 10 years. He was already diagnosed with Pankinson's disease and is receiving allopathy treatment for the same since last 10 years. Here he was given treatment like Abhyanga, Swedana, Matra Basti and Nasya for 21 days. The patient got moderate improvement in his signs and symptoms. It was concluded with the study that Panchakarma therapies has been found beneficial in improving quality of life of patient.

Enhancing Classification of Alzheimer’s Disease using Spatial Attention Mechanism

Aim This study aims to enhance the precision of Alzheimer's disease (AD) detection by integrating Spatial Attention Mechanism into a Convolutional Neural Network (CNN) architecture. Background Alzheimer's disease is a progressive neurodegenerative disorder characterized by abnormal protein deposits in the brain, leading to nerve cell loss and posing a significant global health challenge. Early and accurate detection is crucial for disease management and treatment due to the lack of a cure and the disease's severe progression. Objective The objective of this research is to improve the accuracy of Alzheimer's disease classification using MRI data by implementing a Spatial Attention Mechanism in a CNN architecture. Methods The study utilized T1-weighted MRI data from the OASIS 1 and OASIS 2 datasets. The key innovation is the Spatial Attention layer incorporated within a CNN model, which computes the average of each channel in the input feature map. This layer guides subsequent layers to focus on critical brain regions, enhancing the model's accuracy in differentiating between Alzheimer's disease stages. Results The model achieved a validation accuracy of 99.69% with a sensitivity and specificity of 1.0000, demonstrating its reliability in distinguishing between different stages of Alzheimer's disease. The adaptability of the Spatial Attention layer allows the model to assign higher weights to crucial brain regions, improving its discriminative power. Conclusion The integration of the Spatial Attention Mechanism into the CNN architecture significantly contributes to the early detection of Alzheimer's disease, enabling timely interventions. This innovative approach has the potential to revolutionize Alzheimer's diagnosis by enhancing accuracy and offering a robust solution for classification.

Dazhu Hongjingtian injection attenuated alcohol-induced depressive symptoms by inhibiting hippocampus oxidative stress and inflammation through Nrf2/HO-1/NLRP3 signaling pathway

Ethnopharmacological relevanceAlcoholic depression, a disorder of the central nervous system, is characterized by alcohol abuse, which causes blood-brain barrier disruption and oxidative damage in the brain. The rhizome of Rhodiola crenulate, from which Dazhu Hongjingtian Injection (DZHJTI) is derived, has been traditionally employed in ethnopharmacology to treat neurological disorders due to its neuroprotective, anti-inflammatory, and antioxidant properties. However, the exact mechanism by which DZHJTI alleviates alcoholic depression remains unclear. Aim of the studyThis study aimed to investigate the antidepressant effects of DZHJTI and its underlying mechanisms in a mouse model of alcohol-induced depression. Materials and methodsA model of alcoholic depression was established using C57BL/6J mice, and the effects of DZHJTI on depression-like behaviors induced by alcohol exposure were assessed through behavioral experiments. Histopathological examination was conducted to observe nerve cell damage and microglial activation in the hippocampal region. Oxidative stress indices in the hippocampus, inflammatory factors, and serum levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured using ELISA. Expression of proteins related to the Nrf2/HO-1/NLRP3 signaling pathway was determined by Western blot analysis. ResultsDZHJTI attenuated depression-like behaviors, neuronal cell damage, oxidative stress levels, inflammatory responses, and microglial activation. It also restored levels of brain-derived neurotrophic factor, brain myelin basic protein, DA, and 5-HT in mice with chronic alcohol exposure. After DZHJTI treatment, the expressions of Nuclear Respiratory Factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1) increased in the hippocampus, whereas the levels of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD, cleaved caspase-1, interleukin (IL)-1β, and IL-18 decreased. ConclusionsDZHJTI ameliorates alcohol-induced depressive symptoms in mice through its antioxidant and anti-inflammatory effects, involving mechanisms associated with the Nrf2/HO-1/NLRP3 signaling pathway. This study highlights the potential of DZHJTI as a therapeutic option for alcohol-related depression and suggests the scope for future research to further elucidate its mechanisms and broader clinical applications.

Examining ALS: reformed PCA and random forest for effective detection of ALS

ALS (Amyotrophic Lateral Sclerosis) is a fatal neurodegenerative disease of the human motor system. It is a group of progressive diseases that affects the nerve cells in the brain and spinal cord that control the muscle movement of the body hence, detection and classification of ALS at the right time is considered to be one of the vital aspects that can save the life of humans. Therefore, in various studies, different AI techniques are used for the detection of ALS, however, these methods are considered to be ineffectual in terms of identifying the disease due to the employment of ineffective algorithms. Hence, the proposed model utilizes Modified Principal Component Analysis (MPCA) and Modified Random Forest (MRF) for performing dimensionality reduction of all the potential features considered for effective classification of the ALS presence and absence of ALS causing mutation in the corresponding gene. The MPCA is adapted for capturing all the Low-Importance Data transformation. Furthermore, The MPCA is objected to performing three various approaches: Covariance Matrix Correlation, Eigen Vector- Eigenvalue decomposition, and selecting the desired principal components. This is done in aspects of implying the LI (Lower-Importance) Data Transformation. By choosing these potential components without any loss of features ensures better viability of selecting the attributes for ALS-causing gene classification. This is followed by the classification of the proposed model by using Modified RF by updating the clump detector technique. The clump detector is proceeded by clustering approach using K-means, and the data reduced by their dimension are grouped accordingly. These clustered data are analyzed either for ALS causing or devoid of causing ALS. Finally, the model’s performance is assessed using different evaluation metrics like accuracy, recall, F1 score, and precision, and the proposed model is further compared with the existing models to assess the efficacy of the proposed model.

Metallothionein: A Comprehensive Review of Its Classification, Structure, Biological Functions, and Applications.

Metallothionein is a cysteine-rich protein with a high metal content that is widely found in nature. In addition to heavy metal detoxification, metallothionein is well known as a potent antioxidant. The high sulfhydryl content of metallothionein confers excellent antioxidant activity, enabling it to effectively scavenge free radicals and mitigate oxidative stress damage. In addition, metallothionein can play a neuroprotective role by alleviating oxidative damage in nerve cells, have an anticancer effect by enhancing the ability of normal cells to resist unfavorable conditions through its antioxidant function, and reduce inflammation by scavenging reactive oxygen species. Due to its diverse biological functions, metallothionein has a broad potential for application in alleviating environmental heavy metal pollution, predicting and diagnosing diseases, and developing skin care products and health foods. This review summarizes the recent advances in the classification, structure, biological functions, and applications of metallothionein, focusing on its powerful antioxidant effects and related functions.

The impact of chemical functionalization of carbon nanotubes on the electrochemical performance of carbon fiber/pyrocarbon/carbon nanotube composites as potential materials for electrodes for nerve cell stimulation

In this work, we propose a new carbon–carbon (C–C) composites as a potential materials for electrodes for neural stimulation in neurodegenerative disorders. The C–C composites were made via chemical vapour deposition (CVD) synthesis of pyrocarbon on carbon fibers, with subsequent thermal spray deposition of carbon nanotubes (CNT). Different CNT types were tested to evaluate their impact on electrochemical and biological performance. Materials were analyzed for microstructure, surface chemistry, and electrochemical properties, then tested using SH-SY5Y neuroblastoma cells for biological assessment. TheC–C composites coated with a hydroxy-terminated CNT demonstrated significantly enhanced electrochemical properties, inparticular increased cathodal charge capacity upto12.51mCcm−2, a wide safe potential window of −1.53 to 1.26 V, and decreased impedance, and cut-off frequency (fcut-off = 0.16 kHz). No acute negative biological responses of the materials were detected after 48 h of exposition. Such properties significantly outperform the properties of platinum, which is the basic element of platinum electrodes, demonstrating the excellent performance of the obtained composites and showing it may constitute the basic element of carbon electrodes for nerve stimulation in the future. Our work presents the method for obtaining biologically inert carbon composite micro-electrodes which can potentially be adapted to neural stimulation.

Symptomatic vs. Disease-modifying treatments in neurological diseases: Where next?

Symptomatic vs. Disease-modifying treatments in neurological diseases: Where next? An optimal drug for chronic neurological disease would slow down disease progression in the long term, with short-term symptomatic benefits. This would shorten clinical development timelines and reduce the cost and risk level for drug developers. Henri Huttunen Chief Scientific Officer (CSO) at Herantis Pharma Plc explains. In Parkinson’s disease (PD), the development of motor symptoms is associated with the degeneration of dopamine-producing nerve cells in the midbrain. For decades, motor symptoms of PD have been treated with levodopa, a precursor of dopamine, which helps to replenish dopamine levels in brain areas coordinating movement. Levodopa is an example of a symptomatic treatment as it improves symptoms but does not interfere with the underlying causes or progression of the disease.

The Effect of Al-Qur'an Recitation as Systematic Audio Therapy on Patients with Neurodegenerative Progressive Supranuclear Palsy (PSP): A Review

Al-Quran, as the holy book in the Islamic religion, is not only a spiritual guide but also has a significant psychological impact on the individuals who read it. The Koran offers ethical and moral guidance and covers profound psychological aspects. Its influence is not only limited to religious aspects but also deepens humans' understanding of themselves and their environment. Neurodegenerative disorder refers to a process or condition where nerve cells in the central nervous system (i.e., brain and spinal cord) experience progressive damage or death. The damage leads to decreased cognitive function, behavioral changes, and motor disorders. The present study aims to provide an overview of the effect of listening to Al-Quran recitation as an intervention on neurodegenerative progressive supranuclear palsy (PSP) subjects. The current research used a literature review approach by collecting credible sources in books, scientific articles, documents, and previous research. The findings of this study illustrate that systematic Al-Quran intervention resulted in positive psychological and physiological benefits, especially on the brain's nerves. Thus, frequent, and further medical assistance is imperative for patients with PSP.

Manfaat Herbal Pegagan (Centella Asiatica (L.)) dalam Membantu Mencegah Alzheimer

This community service aims to provide information about the role of Gotu kola extract (Centella asiatica) as a neural antioxidant and mitoprotective in the context of helping reduce symptoms of Alzheimer's disease. Alzheimer's, a form of dementia common in old age, still has no effective treatment after more than a hundred years of research. Gotu kola extract has been traditionally known in Asia as a cognitive-enhancing drug and has antioxidant and mitoprotective properties that can revitalize nerve and brain cells. Through the community service program, we organized a webinar on the benefits of Gotu Kola herbs in helping prevent Alzheimer's disease for students of the University of 17 August 1945 Jakarta and the general public in North Jakarta. The results of this activity showed a positive response from participants, with 42 participants from various backgrounds attending the webinar.

Esophageal viral and bacterial microbiome unbalances characterize achalasia

Achalasia is a rare neuromuscular disorder of the esophagus whose pathogenesis is poorly understood. It is characterized by the loss of nerve cells in the esophagus, failure of the lower esophageal sphincter to relax, and impaired esophageal peristalsis. In this study, we re-analyzed transcriptomics data from blood and esophageal tissue samples of achalasia patients publicly available. Blood analysis showed hyperactivation of the immune system and dysfunction of the nervous system, consistent with the hypothesis of immune-mediated pathogenesis leading to neuronal loss. Mucosal tissue analysis e showed a remarkable unbalance in virome and bacteriome compositions in achalasia. In particular, bacterial diversity was reduced across the esophagus in achalasia compared to healthy controls, and in the distal esophagus bacteria associated with the healthy state, such as Firmicutes, Tenericutes, and Bacteroidetes, were less represented if not completely absent. Importantly, the only other component of the microbiota that varied significantly between achalasia and controls was the virome. Bacteriophages that parasite Firmicutes were strongly enriched in the esophagus supporting a predator-prey interaction. In conclusion, our study opens new horizons on a circulating signature of achalasia and the role of viral-bacterial interactions in orchestrating mucosal homeostasis and possibly disease pathogenesis. Key summaryAchalasia is a rare swallowing disorder with unknown causes. The role of gut microbiota, especially viruses, in achalasia is unclear. This study investigated the differences in viral and bacterial communities between achalasia patients and healthy people, and how they affect the esophageal mucosa. The findings may help develop new diagnostic tools and therapies based on novel hypotheses about the pathogenesis of achalasia.

Cerebral arterial blood flow, attention, and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.

Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension, and surgery is currently the main treatment for hypertensive cerebral hemorrhage, but the bleeding caused by surgery will cause damage to the patient's nerve cells, resulting in cognitive and motor dysfunction, resulting in a decline in the patient's quality of life. To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage. Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group, while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group. The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test (WCST) and cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The Hamilton Depression Rating Scale (HAMD-24) was used to evaluate the severity of depression of involved patients. Cerebral arterial blood flow was measured in both groups. The MoCA score, net scores I, II, III, IV, and the total net score of the scratch test in the observation group were significantly lower than those in the control group (P < 0.05). Concurrently, the total number of responses, number of incorrect responses, number of persistent errors, and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group (P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery was significantly lower in the observation group than in the control group (P < 0.05). The basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score (P < 0.05), and negatively correlated with each part of the WCST test (P < 0.05). In the observation group, the post-treatment improvement was more prominent in the Paddle Pin test, WCST test, HAMD-24 score, and MoCA score compared with those in the pre-treatment period (P < 0.05). Blood flow in the basilar artery, left middle cerebral artery, right middle cerebral artery, left anterior cerebral artery, and right anterior cerebral artery significantly improved in the observation group after treatment (P < 0.05). Impaired attention, and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Study on chemical characterization and sleep-improvement function of Prunella vulgaris L. based on the functional components

Prunella vulgaris L. (P. vulgaris) has great application value and development prospects in improving sleep. In this study, we continued to evaluate the sleep-improvement function and mechanism of P. vulgaris from both chemical characterization and function based on sleep-improvement functional ingredients, rosmarinic acid and salviaflaside, screened out in the previous stage as the index components. The chemical constituents of P. vulgaris and its phenolic acid fraction were characterized by the UPLC-MSn technology. The quality of the sleep-improvement phenolic acid fraction of P. vulgaris was scientifically evaluated by fingerprints combined with quantitative analysis of rosmarinic acid and salviaflaside. The function of phenolic acid parts of P. vulgaris in improving sleep was verified by different insomnia models including the PCPA-induced insomnia model and surface platform sleep deprivation model. HE staining was used to observe the effect of P. vulgaris on the morphology of nerve cells in different brain regions. In vivo experiments and molecular docking explored the sedative-hypnotic effects of functional ingredients of P. vulgaris. All these results investigated the material basis and mechanism of P. vulgaris to improve sleep from multiple perspectives, which contribute to providing a basis for the development of functional food to improve sleep.

Perspektif Al-Qur’an Tentang Sel Saraf Dalam Kajian Integrasi Agama Dan Sains

Humans are God's perfect creation. Perfection lies in reason. Apart from intelligence, humans also have a brain as the control center for all human activities. The aim of this research is to examine and discover more deeply about human nerve cells from the perspective of the Koran. This research uses qualitative methods and produces descriptive data through a literature approach. The main sources start from secondary sources including books or journals related to the concept of nerve cells according to religious and scientific views. There are several verses scattered in the surahs of the Koran regarding nerve cells. The word "Naashiyah" in this verse means forelock. Scientific facts about the crown is the part of the forebrain that functions as a controller, memory and decision maker, which is known as Frontal lobe. The information from these verses is true that the forelock is the place where decisions are made and is the measuring point for right or wrong decisions taken. Therefore, Al-Quran information and scientific facts from research results are integrated with each other and show harmony.

Effect of kynurenic acid on enzymatic activity of the DNA base excision repair pathway in specific areas of the sheep brain

Relatively low levels of antioxidant enzymes coupled with high oxygen metabolism result in the formation of numerous oxidative DNA damages in the tissues of the central nervous system. Recently, kynurenic acid (KYNA), knowns for its neuroprotective properties, has gained increasing attention in this context. Therefore, our hypothesis assumed that increased KYNA levels in the brain would positively influence mRNA expression of selected enzymes of the base excision repair pathway as well as enhance their efficiency in excising damaged nucleobases in specific areas of the sheep brain. The study was conducted on adult anestrous sheep (n = 18), in which two different doses of KYNA (20 and 100 μg/day) were infused into the third brain ventricle for three days. Molecular and biochemical analysis included the hypothalamus (preoptic and mediol-basal areas), hippocampus (CA3 field) and amygdala (central amygdaloid nucleus), dissected from the brain of sheep euthanized immediately after the last infusion. The results revealed a significant increase P < 0.001) in the relative mRNA abundance of N-methylpurine DNA glycosylase (MPG) following administration of both dose of KYNA across all examined tissues. The transcription of thymine-DNA glycosylase (TDG) increased significantly (P < 0.001) in all tissues in response to the lower KYNA dose compared to the control group. Moreover, 8-oxoguanine (8-oxoG) DNA glycosylase (OGG1) mRNA levels were also higher in both animal groups (P < 0.001). In addition, in the hypothalamus, hippocampus and amygdala, AP endonuclease 1 (APE1) mRNA expression increased under both doses of KYNA. Moreover, the both dose of KYNA significantly stimulated the efficiency of 8-oxoG excision in hypothalamus and amygdala (P < 0.05–0.001). The lower and higher doses of KYNA significantly influenced the effectiveness of εA and εC in all structures (P < 0.01–0.001). In conclusion, the favorable effect of KYNA in the brain may include the protection of genetic material in nerve and glial cells by stimulating the expression and efficiency of BER pathway enzymes.

Adenosine signalling to astrocytes coordinates brain metabolism and function

Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply1,2. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism3,4, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood5,6. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. Stimulation of A2B receptors recruits the canonical cyclic adenosine 3′,5′-monophosphate–protein kinase A signalling pathway, leading to rapid activation of astrocyte glucose metabolism and the release of lactate, which supplements the extracellular pool of readily available energy substrates. Experimental mouse models involving conditional deletion of the gene encoding A2B receptors in astrocytes showed that adenosine-mediated metabolic signalling is essential for maintaining synaptic function, especially under conditions of high energy demand or reduced energy supply. Knockdown of A2B receptor expression in astrocytes led to a major reprogramming of brain energy metabolism, prevented synaptic plasticity in the hippocampus, severely impaired recognition memory and disrupted sleep. These data identify the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.

Pioneers of cortical cytoarchitectonics: the forgotten contribution of Herbert Major

The study of cortical cytoarchitectonics and the histology of the human cerebral cortex was pursued by many investigators in the second half of the nineteenth century, such as Jacob Lockhart Clarke, Theodor Meynert, and Vladimir Betz. Another of these pioneers, whose name has largely been lost to posterity, is considered here: Herbert Coddington Major (1850–1921). Working at the West Riding Asylum in Wakefield, United Kingdom, Major’s thesis of 1875 described and illustrated six-layered cortical structure in both non-human primates and man, as well as “giant nerve cells” which corresponded to those cells previously described, but not illustrated, by Betz. Further journal publications by Major in 1876 and 1877 confirmed his finding of six cortical strata. However, Major’s work was almost entirely neglected by his contemporaries, including his colleague and sometime pupil at the West Riding Asylum, William Bevan-Lewis (1847–1929), who later (1878) reported the presence of both pentalaminar and hexalaminar cortices. Bevan-Lewis’s work was also later credited with the first illustration of Betz cells.